Herbal products are being increasingly used in the United States: 15 million people are at risk for drug interactions with the herbal products. Some of these products affect the immune system but have not been studied in the context of transplantation. We plan to understand the mechanisms of action of selected botanicals in transplantation and the interactions between immunosuppressive drugs and botanicals, taking advantage of the old Eastern herbal knowledge. We have studied several commonly used herbal products and found that some suppress and others stimulate lymphocyte proliferation in vitro. We have focused on two products; ginger which suppresses and milk thistle which stimulates the proliferation of lymphocytes challenged with mitogens and all antigens. These effects are consistently observed in human and murine lymphocytes. The mechanism of suppression and stimulation appears to be increased secretion of Th2 and Th1 cytokines by Ginger and Milk thistle respectively. We have started to study the effect of Ginger in a mouse model of cardiac transplantation. Our hypothesis is that naturally occurring herbal products can modulate the immune system and that these products will be clinically useful because of their holistic actions and low toxicities. More specifically, we hypothesize that ginger will suppress and milk thistle will stimulate the immune reaction in vivo against all antigens including those in cardiac allografts. We will test this hypothesis by using standardized preparations of these herbs in a clinically relevant model of cardiac transplantation in mice. We expect that ginger will prolong survival of the allografts while milk thistle will shorten the survival of these grafts. We also propose to the test the interaction of these two herbs with conventional immunosuppressive drugs like cyclosporine A in the model of cardiac allografts. Our experiments will determine, holistically, if herbal products modulate transplant immunity. They will also uncover the mechanisms of action of Ginger and Milk thistle, determine if these herbal products interact with conventional immunosuppressive drugs, and potentially discover novel immunomodulatory agents.